Ibhazehiebo K, Iyawe V I, Koibuchi Noriyuki
Department of Physiology, School of Basic Medical Sciences, College of Medical Sciences, University of Benin, Benin-City.
Niger J Physiol Sci. 2013 Dec 20;28(2):115-20.
Methamidophos is a toxic organophosphorus compound that inhibits acetlycholinesterase activity, and induces neurotoxicity. It is a synthetic chemical commonly used as pesticides to limit pest damages to cultivated plants. Currently, there is serious public health concern over its safety and use due to its global nature, persistence and bioaccumulations. We have previously reported that methamidophos suppressed thyroid hormone receptor (TR)-mediated transcription, but did not dissociate the interaction between TR and its response element (thyroid hormone response element; TRE), neither did it interact with nuclear cofactors. In the present study, we investigated the effects of methamidophos on cerebellar neuronal cells. Using primary cerebellar culture from new born rats, We observed that Purkinje cell dendrite arborization were greatly impaired in the absence of thyroid hormone (TH), However, low dose methamidophos 10-6 M did not significantly impair dendrite arborization of cerebellar Purkinje cells in the presence of thyroid hormone (TH). However, using granule cell reaggregate culture, we observed that low dose methamidophos 10-6 M remarkably suppressed granule cell neurite extension in the presence of TH. Taken together, our study shows that low dose methamidophos may negatively impact TH-mediated cerebellar neuronal cell development and function, and consequently could interfere with TH-regulated neuronal events.
甲胺磷是一种有毒的有机磷化合物，它会抑制乙酰胆碱酯酶的活性，并诱发神经毒性。它是一种合成化学品，常用作杀虫剂以减少害虫对栽培植物的损害。目前，由于其全球性、持久性和生物累积性，其安全性和使用引起了严重的公共卫生关注。我们之前曾报道，甲胺磷会抑制甲状腺激素受体（TR）介导的转录，但不会使TR与其反应元件（甲状腺激素反应元件；TRE）之间的相互作用解离，它也不会与核辅因子相互作用。在本研究中，我们调查了甲胺磷对小脑神经元细胞的影响。利用新生大鼠的原代小脑培养物，我们观察到在没有甲状腺激素（TH）的情况下，浦肯野细胞树突分支严重受损。然而，在存在甲状腺激素（TH）的情况下，低剂量的甲胺磷（10-6 M）并没有显著损害小脑浦肯野细胞的树突分支。然而，使用颗粒细胞重聚集培养，我们观察到在存在TH的情况下，低剂量的甲胺磷（10-6 M）显著抑制了颗粒细胞的神经突延伸。综上所述，我们的研究表明，低剂量的甲胺磷可能会对TH介导的小脑神经元细胞发育和功能产生负面影响，进而可能干扰TH调节的神经元活动。
